Oral microorganisms colonizing the tooth surface and gingival sulcus are acknowledged to be the primary cause of periodontitis. This research project is aimed at identifying and characterizing the chemical mediators and cellular mechanisms responsible for the loss of tooth-supporting tissue so characteristic of this disease. Studies are in progress or will be initiated to approach the following specific aims: 1. identification of bacterial products which can directly stimulate bone resorption. Bacteria associated with periodontal disease are being tested for products which can stimulate resorption of cultured bone rudiments. A soluble material from Actinomyces viscosus has been found which is a potent stimulator in this model system; its chemical nature is now being investigated. Lipopolysaccharide preparations from various Gram-negative organisms isolated from deep periodontal pockets will be tested and compared for bone resorptive potential. 2. identification of factors which can stimulate macrophage secretion of collagenase. Macrophages are consistently found in the chronic inflammatory lesion of periodontitis. A material prepared from Actinomyces viscosus has been found which stimulates cultured macrophages to secrete collagenase. This factor and its action on macrophages will be further evaluated. Products from other bacteria will be similarly examined using this model. 3. identification of the cellular source of osteoclast activating factor (OAF). OAF is a material produed by activated peripheral blood mononuclear cells which can stimulate bone resorption in vitro. Using enriched populations of cultured lymphocytes and macrophages, experiments will be conducted to determine which of these cells produces OAF and the nature of the cellular interactions which occur.